Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal Task.

The overall goal of this experiment is to quantify primary motor cortex excitability and inhibition during a motor response inhibition task by using transcranial magnetic stimulation, also known as TMS. This method can help answer key questions in the field of motor control research to understand cortical physiologic changes during motor task completion and response inhibition. The main advantage of this technique is the use of non-invasive transcranial magnetic stimulation technology to explore primary motor cortex physiology during a child friendly stop signal behavioral task.

This method can provide insight into pediatric movement disorders. It can also be applied to any neuro-psychiatric conditions that affect motor regulation, such as attention deficit hyperactivity disorder and autism spectrum disorder. Demonstrating the procedure will be David Huddleston and Alyssa Roeckner from our laboratory.

Begin by screening the participant for TMS contraindications using a standardized questionnaire. Demonstrate how TMS works by delivering a magnetic pulse over the operator's own forearm. After that, deliver a TMS pulse over the participant's forearm, so that he or she can feel the pulse.

Then, place earplugs in participant's ears for hearing protection. Next, have the subject abduct the dominant index finger to identify the first dorsal interosseous muscle, or FDI. Place the negative electrode over the belly of the FDI, then place the positive electrode between second and third metacarpophalangeal, or MCP joints, and the ground electrode over the fifth MCP joint.

Position the participant's hands with ulnar aspects of both arms and hands resting fully on a pillow with no anti-gravity effort required. Finally, have the participant extend the dominant index finger while the third through fifth fingers flexed. Then, place a game controller pad on the pillow, so that the index finger rests on the button you use for the race car Slater-Hammel task.

Begin by obtaining base line TMS measurements, using a 90 millimeter circular TMS coil positioned tangentially to the skull over the vertex with the handle pointing towards the occiput to produce an induced posterior to anterior current over M1.Then, use a wax pencil to mark the scalp location once the hot spot was located to ensure that the TMS pulse delivery occurs at the same cortical region. Perform 20 trials of baseline single pulse TMS induced FDI MEPs using an intensity of 120%of resting motor threshold, abbreviated as RMT, with both hands at rest. Finally, perform 20 trials of baseline paired pulse TMS measures of M1 short interval intracortical inhibition at rest using interstimulus interval of three milliseconds.

Begin by displaying the race car Slater-Hammel response inhibition task on a monitor directly in front of the participant. Start the experiment by first training the participant on the behavioral task, by telling the subject that the car on the left side of the monitor will begin to move after the button is pressed by adduction of the dominant index finger. Then, tell the participant that the goal for go trials is to lift the finger as close to, but before, the 800 millisecond target, as depicted by a vertical line on the screen.

Have the participant practice 10 go trials. Next, provide training for the stop task, by telling the participant that the second set of trials involves the car randomly stopping before the 800 millisecond target. Tell the child to keep his index finger on the button, without lifting the finger, whenever the car randomly stops.

Inform the participant that if stop signal is presented, and finger is lifted before the checkered flag, a too soon"message will appear. Tell the child that a great"message will be displayed after successful stop trials. Have the child practice 10 stop trials.

After the participant practices the go only and stop only trials, tell them the next practice block contains a mixture of go and stop trials. Have the child perform 20 trials of mixed go and stop as a final practice. Next, in preparation of the actual online Slater-Hammel experiment, remind the participant to push down the dominant index finger to start the trail, to lift off the finger for go trials, and keep their finger on the button for stop trials.

Tell the child that TMS pulses will be delivered during the Slater-Hammel task, and that there will be three blocks of online Slater-Hammel TMS trials. Place the 90 millimeter circular coil over the vertex using previous wax pencil mark to preferentially stimulate dominant M1 and set the conditioning pulse intensity to 60%RMT and test pulse to 120%RMT. Finally, begin the online Slater-Hammel TMS experiment.

Here, representative neurophysiologic data in different trial conditions using least squares mean estimates calculated from the regression model. For MEP amplitudes, the independent variables sex, sight, and trial block, were not significant in the regression model. The TMS pulse condition and its interaction with trial condition were significant.

All pairwise comparisons of single pulse MEP amplitudes between the three task conditions were insignificant. However, the differences between go versus failed stop and successful versus failed stop were significant. Once mastered, this technique can be done in approximately one hour if it is performed properly.

While attempting this procedure, its important to remember to instruct the children how to correctly perform during the Slater-Hammel task. The set up of EMG leads and the technique used during data acquisition are important for obtaining reliable data. Following this procedure, other methods like using two TMS coils simultaneously during behavioral task can be performed in order to explore how other cortical regions regulate the motor system during motor tasks.

After its development, this technique paved the way for researchers in the field of motor control research to explore motor system physiology in patients with motor control problems such as Tourette's Syndrome, Dystonia, ADHD, and autism spectrum disorder. After watching this video, you should have a good understanding of how to perform TMS in children during a behavioral task.